SMAD4 and cancer: SMAD genes are located in four chromosomes (4, 13, 15, and 18), and three of them, SMAD2, SMAD4, and SMAD7, are clustered in the 18q21.1 region, frequently deleted in cancers; three of them, SMAD3, SMAD6, and SMAD5, are clustered in chromosome 15 (SMAD3 and SMAD6 in region 15q21–22, and SMAD5 in region 15q31); and SMAD1 and SMAD8 are located in chromosomes 4 and 13.